Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors.

Abstract

We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 microg/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor.

• Authors: D W Laske, R J Youle, E H Oldfield
• Journal: Nature medicine (Nat Med) Vol. 3 Issue 12 Pg. 1362-8 (Dec 1997) ISSN: 1078-8956 [Print] United States
• PMID: 9396606 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Diphtheria Toxin
• Transferrin

Topics

• Adult
• Aged
• Antibodies (blood)
• Brain (metabolism, pathology)
• Brain Neoplasms (pathology, therapy)
• Diphtheria Toxin (adverse effects, genetics, therapeutic use)
• Drug Design
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Transferrin (adverse effects, genetics, therapeutic use)